Surfactant-free, self-assembled iron oxide/silica core–shell (SAIO@SiO2) nanocarriers were synthesized as bifunctional magnetic vectors that can be triggered for the controlled release of therapeutic agents by an external magnetic field. In addition, drug release profiles can be well-regulated through an ultrathin layer of silica shell. The hydrophobic drug molecules were encapsulated within the iron oxide-PVA core and then further covered with a thin-layer silica shell to regulate the release pattern. Remote control of drug release from the SAIO@SiO2 nanocarriers was achieved successfully using an external magnetic field where the core phase being structurally disintegrated to a certain extent while subjected to magnetic stimulus, resulting in a burst release of the encapsulated drug. However, a relatively slow and linear release restored immediately, directly after removal of the stimulus. The nanostructural evolution of the nanocarriers upon the stimulus was examined and the mechanism for controlled drug release is proposed for such a core–shell nanocarrier. Surprisingly, the surfactant-free SAIO@SiO2 nanocarriers demonstrated a relatively high uptake efficiency from the HeLa cell line. Together with a well-regulated controlled release design, the nanocarriers may provide great advantages as an effective cell-based drug delivery nanosystem for biomedical applications.